Objective To analyze the influence of clinical indicators and PPARD gene polymorphism on the hypoglycemic efficacy of dapagliflozin(DAPA)in patients with type 2 diabetes mellitus(T2DM).Methods A total of 102 patients with T2DM who visited the Affiliated Hospital of Jiangnan University and the Affiliated Hospital of Xuzhou Medical University from June 2021 to December 2023 were selected as the study subjects,an observational cohort of T2DM patients treated with DAPA was established,and DAPA tablets of 10 mg were administered orally once a day for 12 weeks,the venous blood and clinical data of the patients were col-lected.PPARD gene polymorphism typing was performed by using the Snapshot method.The differences in clinical indicators among patients with different genotypes were compared and the influencing factors of DA-PA in improving insulin resistance index(HOMA-IR)were analyzed.Results Eighty-two patients completed the 12-week follow-up.Before DAPA treatment,the differences in the clinical indicators of patients with dif-ferent PPARD rs3777744 genotypes were not statistically significant(P＞0.05).After 12 weeks of DAPA treatment,compared with patients with AA genotype,patients carried of G allele(GG+AG genotype)had lower levels of fasting blood glucose(FPG),HOMA-IR and its decrease,and the differences were statistically significant(P＜0.05).The results of multiple linear regression analysis showed that the genotype of PPARD rs3777744 locus and baseline HOMA-IR were correlated with the improvement of HOMA-IR after 12 weeks of DAPA treatment,and the improvement of HOMA-IR in G allele carriers was not as significant as that in AA genotype patients,and the higher the baseline HOMA-IR,the more significant the improvement of HO-MA-IR.Conclusion Different genotypes of PPARD rs3777744,baseline HOMA-IR are important influencing factors for DAPA to improve insulin resistance of T2DM patients.

Objective To explore the effects of fecal microbiota transplantation on blood uric acid(UA)metabolism,adverse reactions,and gout control in patients with refractory gout.Methods A total of 102 patients with refractory gout in the First Affiliated Hospital of Medical College of Shantou University from June 2020 to June 2023 were randomly divided into two groups,with 51 cases in each group.Control group received benzbromarone and febuxostat treatment,while the observation group re-ceived fecal microbiota transplantation.The gout control status and occurrence of adverse reactions were observed in both groups;intestinal flora,UA,levels of C-reactive protein(CRP),interleukin-18(IL-18),interleukin-6(IL-6),and scores of joint pain,swelling and limited mobility were compared between the two groups before and after treatment.Results Five patients in each group were lost to follow-up.The total gout control rate in the observation group was 89.13％,which was significantly higher than 69.57％ in the control group(P＜0.05).At 4 and 12 weeks after treatment,the levels of Escherichia coli,UA,CRP,IL-18 and IL-6 as well as the scores of joint swelling,pain and limited mobility in the observation group were significantly lower than those in the control group,while the lev-els of Bifidobacterium,Lactobacillus and Bifidobacterium to Escherichia coli(B/E)ratio were signifi-cantly higher than those in the control group(P＜0.01).The total incidence of adverse reactions was 10.87％ in the observation group and 6.52％ in the control group,with no significant between-group difference(P＞0.05).Conclusion Fecal microbiota transplantation has a definite therapeutic effect for patients with refractory gout,which can significantly reduce UA level and control clinical symptoms,and its mechanism may be related to the correction of intestinal flora imbalance.

Objective:To investigate the efficacy and safety of different transcatheter arterial chemoembolization(TACE)-based regimens in patients with unresectable hepatocellular carcinoma(uHCC)and explore the optimal timing for combining TACE with tyrosine kinase inhibit-ors(TKIs)and immune checkpoint inhibitors(ICIs).Methods:A retrospective analysis was conducted on data from 555 patients with uHCC who underwent TACE-based treatment between April 2016 and December 2021 in Nanfang Hospital,Southern Medical University.The pa-tients were assigned into the following four groups according to different treatment regimens:TACE group(n=317),TACE combined with TKIs group(TACE+TKIs,n=66),TACE combined with ICIs group(TACE+ICIs,n=33),and TACE combined with TKIs+ICIs group(TACE+TKIs+ICIs,n=139).Subgroup analysis was performed within the TACE+TKIs+ICIs group,with patients being assigned into"pre-TACE"and"post-TACE"groups based on the timing of the combination therapy.Univariate and multivariate Cox regression analyses were conducted to identify pro-gnostic factors influencing overall survival(OS).Results:The TACE+TKIs+ICIs group showed the longest OS(21.9 months,95%confidence in-terval[CI]:17.2-26.6,P=0.030)and progression-free survival(PFS)(8.3 months,95%CI:7.3-9.3,P=0.004)compared to those in the other three groups.In the subgroup analysis,the"post-TACE"group had longer OS than the"pre-TACE"group(26.8 months vs.19.2 months,P = 0.011).The objective response rate(ORR)was 32.8%,41.1%,42.4%,and 52.5%(P=0.001)and the disease control rate(DCR)was 59.6%,71.2%,69.7%,and 82.7%(P<0.001)in the TACE,TACE+TKIs,TACE+ICIs,and TACE+TKIs+ICIs groups,respectively.The adverse events were similar to those reported in previous studies.Cox regression analysis revealed that tumor number,extrahepatic metastasis,and treatment regimen were independent factors influencing OS in patients(all P<0.05).Conclusions:TKIs or ICIs can improve OS and PFS in patients with uHCC receiving TACE,and the combination of TKIs+ICIs with TACE achieves better beneficial outcomes.The greatest OS was observed when the combination therapy TKIs+ICIs was initiated within 3 months after the first TACE procedure.

OBJECTIVE: The present study aimed to evaluate the therapeutic effect and explore the underlying mechanisms of Longxue Tongluo Capsule (LTC) on ischemic stroke rats. METHODS: Twenty-six rats were randomly divided into four groups, including sham group, sham + LTC group, MCAO group, and MCAO + LTC group. Ischemic stroke rats were simulated by middle cerebral artery occlusion (MCAO), and LTC treatment group were orally administrated with 300 mg/kg of LTC once daily for seven consecutive days. LTC therapy was validated in terms of neurobehavioral abnormality evaluation, cerebral infarct area, and histological assessments. The plasma metabolome comparisons amongst different groups were conducted by UHPLC-Q Exactive MS in combination with subsequent multivariate statistical analysis, aiming to finding the molecules in respond to the surgery or LTC treatment. RESULTS: Intragastric administration of LTC significantly decreased not only the neurobehavioral abnormality scores but also the cerebral infarct area of MCAO rats. The interstitial edema, atrophy, and pyknosis of glial and neuronal cells occurred in the infarcted area, core area, and marginal area of cerebral cortex were improved after LTC treatment. A total of 13 potential biomarkers were observed, and Youden index of 11 biomarkers such as LysoPC, SM, and PE were more than 0.7, which were involved in neuroprotective process. The correlation and pathway analysis showed that LTC was beneficial to ischemic stroke rats via regulating glycerophospholipid and sphingolipid metabolism, together with nicotinate and nicotinamide metabolism. Heatmap and ternary analysis indicated the synergistic effect of carbohydrates and lipids may be induced by flavonoid intake from LTC. CONCLUSION The present study could provide evidence that metabolomics, as systematic approach, revealed its capacity to evaluate the holistic efficacy of TCM, and investigate the molecular mechanism underlying the clinical treatment of LTC on ischemic stroke.

Objective To establish the immortalized cell lines of peripheral blood lymphocytes for old male residents in high background radiation area(HBRA)in Guangdong,China,in order to preserve the specific genomic resources of residents in HBRA for the further genetic and molecular biological study on HBRA.Methods The peripheral blood samples of 20 old male residents in HBRA were collected after informed consent.The immortalized B lymphoblastoid cell lines,2 for each resident,were established with Epstein-Barr virus.After being frozen and recovered,the cell viability,the contamination of bacterium and mycoplaama were analyzed.The stabilization of cell lines was decided by comparing the karyotypes of the peripheral blood lymphocytes and the cell lines.Results 40 cell lines for 20 residents in HBRA were successfully established.The recovery rate of cell lines after being frozen was 100%.All the cell viablity after recovery was higher than 90%.and no contamination of bacteria and mycoplasma occurred.The karyotypes of the 20th generation cell lines were not change.Conclusion The immortalized cell lines established in this study could provide biological resources for further study on genetics and molecular biology in HBRA.

Objective To study the changes of the transient outward K+ current (Ito),delayed rectifier K+ current(IkDR) and the inward rectifier K+ current(Ik1) of the rat bone mesenchymal stem cells (MSCs) induced by 5-Azacytidine(5-Aza) during proliferating and differentiating process in vitro. Methods MSCs were cultured according to related articles for two weeks and then some of the cells were induced by 5-Azacytidine.The experiment was divided into uninduced(cultured for 6w) and induced(1,2,3 and 4w) cell groups. Each week had twenty cells random tested by the whole-cell patch clamp technology and the K+ currents were identified by corresponding ionic blockers.Results The detection rate of the same type of K+ current during test weeks had no significant deviation;The three types of K+ current intensity were gradually augmented after being inducing cultured for 1,2,3 and 4 weeks(P

Defensin is a kind of antimicrobiol and cytotoxic peptides which have been found in a large range of living organisms. The mammal defensins have the most wide range antimicrobiol spectrum. The distribution, structure, gene expression regulation of mammal defensins in China and abroad were summarized. Its application on medicine and plant resistant gene engineering were prospected.